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Central amygdala CRF1 cells control nociception and anxiety-like behavior

Neuropsychopharmacology volume 49, pages 341–342 (2024)Cite this article

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The central amygdala (CeA) modulates affective states and adaptive behaviors, under both normal and pathological conditions. Rodent studies show that cells in the CeA express a variety of neuropeptides and neuropeptide receptors that modulate the activity of CeA cells. The neuropeptide corticotropin-releasing factor (CRF) and CRF type-1 receptors (CRF1) are densely expressed in the CeA [1]. CRF binds CRF1 with high affinity, and a large corpus of pharmacology studies show that this signaling event in the CeA promotes anxiety- and pain-related behaviors [2].

Translational researchers have been exploring the therapeutic potential of CRF1 antagonists for many years, but clinical trials in patients with anxiety, depression, and/or alcohol use disorder have largely yielded negative results (please see ref. [3] for a discussion on potential avenues for advancing CRF1 antagonists as therapeutics) [3, 4]. Although the efficacy of CRF1 antagonists in pain management remains untested, the lack of success of these compounds in managing anxiety and related conditions in humans highlight the need for expanding our understanding of how the CRF system modulates these behaviors in model animals and humans. Work in our lab is currently focused on elucidating the role of specific subpopulations of CRF1 cells in stress-, pain- and addiction-related behaviors in rats. To this end, we recently developed CRF1-Cre rats that permit visualization and manipulation of specific populations of CRF1 cells [1]. Using these animals, we showed that in vivo stimulation of CeA CRF1 cells increases anxiety-like behavior and produces allodynia [1]. This finding suggests that therapeutic strategies aimed at modulating the activity of CRF1 cells (but not necessarily CRF1 receptors) may be useful for managing anxiety and pain-related states and behaviors.

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References

  1. Weera M, Agoglia A, Douglass E, Jiang Z, Rajamanickam S, Shackett R, et al. Generation of a CRF1-Cre transgenic rat and the role of central amygdala CRF1 cells in nociception and anxiety-like behavior. eLife. 2022;11:e67822.

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Funding

This work was supported by NIH grants AA029726 (MMW), AA023305 (NWG), AA026531 (NWG), AA025792 (NWG), AA028727 (NWG) and in part by a Merit Review Award BX003451 (NWG) from the United States (U.S.) Department of Veterans Affairs, Biomedical Laboratory Research and Development Service.

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Authors and Affiliations

  1. Department of Physiology, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA, 70112, USA

    Marcus M. Weera & Nicholas W. Gilpin

  2. Neuroscience Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, LA, 70112, USA

    Nicholas W. Gilpin

  3. Southeast Louisiana VA Healthcare System, New Orleans, LA, 70119, USA

    Nicholas W. Gilpin

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  1. Marcus M. Weera
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MMW and NWG wrote the paper.

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Correspondence to Marcus M. Weera.

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Competing interests

Dr NWG owns shares in Glauser Life Sciences, Inc., a company with interest in developing therapeutics for mental health disorders. There was no direct link between those interests and the work contained herein. Dr MMW has nothing to disclose.

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Weera, M.M., Gilpin, N.W. Central amygdala CRF1 cells control nociception and anxiety-like behavior. Neuropsychopharmacol. 49, 341–342 (2024). https://doi.org/10.1038/s41386-023-01693-2

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  • DOI: https://doi.org/10.1038/s41386-023-01693-2

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